Potential of N-acetylcysteine as treatment for the adult respiratory distress syndrome.
The adult respiratory distress syndrome (ARDS), often referred to as non-cardiac pulmonary oedema, is now regarded as a very complicated inflammatory process with oedema being only one facet. In recognition of this, pharmacologic therapy with anti-inflammatory corticosteroids was used widely until the completion of randomized clinical trials. Unfortunately, corticosteroids have not been proved to be useful in preventing ARDS in septic patients nor in patients with established ARDS and this has led to investigations with pharmacologic agents which are safer and more specifically targeted to certain parts of the inflammatory process. We have examined the role of the glutathione anti-oxidant system in the sheep model of ARDS as well as in patients with established ARDS through use of intravenous N-acetylcysteine (NAC). We have found that the response to endotoxin is markedly blunted in sheep treated with NAC. In our controlled clinical trials with NAC we found that patients with ARDS have depressed plasma and red cell glutathione concentrations, that these levels are substantially increased by therapy with intravenous NAC and there are measurable clinical responses to treatment with regard to increased oxygen delivery, improved lung compliance and resolution of pulmonary oedema.
Bernard
G R
GR
Division of Pulmonary and Intensive Care Medicine, Vanderbilt University, Nashville, TN 37232.
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D004311:Double-Blind Method; D005609:Free Radicals; D005978:Glutathione / Q000097:blood; D006801:Humans; D008213:Lymphocyte Activation; D008775:Methylprednisolone / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D012756:Sheep
D005609:Free Radicals; D005978:Glutathione; D000111:Acetylcysteine; D008775:Methylprednisolone